The type III TGF-beta receptor regulates epithelial and cancer cell migration through beta-arrestin2-mediated activation of Cdc42.

Journal Article

Loss of expression of the TGF-beta superfamily coreceptor, the type III TGF-beta receptor (TbetaRIII or betaglycan), occurs in a broad spectrum of human cancers including breast, lung, ovarian, pancreatic, prostate, and renal cell cancer. TbetaRIII suppresses cancer progression in vivo, at least in part, by reducing cancer cell motility. However, the mechanism by which TbetaRIII regulates migration is unknown. Here, we demonstrate an unexpected TGF-beta signaling independent role for TbetaRIII in activating Cdc42, altering the actin cytoskeleton and reducing directional persistence to inhibit random migration of both cancer and normal epithelial cells. Functionally, TbetaRIII through its interaction with the scaffolding protein beta-arrestin2, activates Cdc42 and inhibits migration. These studies identify a TGF-beta independent homeostatic function for TbetaRIII in regulating cell migration.

Full Text

Duke Authors

Cited Authors

  • Mythreye, K; Blobe, GC

Published Date

  • May 19, 2009

Published In

Volume / Issue

  • 106 / 20

Start / End Page

  • 8221 - 8226

PubMed ID

  • 19416857

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.0812879106

Language

  • eng

Conference Location

  • United States